Major Histocompatibility Complex Class I: Difference between revisions

A recent study called ''Targeting a neoantigen derived from a common TP53 mutation'' describes the means by which T Cell Receptor mimic (TCRm) antibodies were created a new class of immunotherapy. TP53, tumor protein 53, is a tumor suppressor gene, and is the most commonly mutated protein in cancers. Most [[P53]] is located inside the cell, the largest concentration is in the nucleus, which makes it difficult to find a treatment for TP53. Scientists have been struggling to design a drug to target this inactivated tumor suppressor gene. However, a  small percentage is degraded by proteasomes and is present on the cell surface by MHC, Human Leukocyte Antigen (HLA). The most frequent mutation in the TP53 gene is a substitution from Arginine to Histidine at codon 175 (R175H). Most mutations within this gene occur as single-nucleotide variants at positions nearest to the DNA-binding domain. Using an HLA TP53 complex researchers discovered that neoantigen p53R175H is displayed by HLA:A2 on the cell surface at very low density. These peptide-HLA (pHLA) complexes are naturally ligands for T-cell receptors (TCRs). The advantage of using TCRm’s for immunotherapies is that they are of higher affinity for pHLA and are more easily converted to different therapeutics when compared to their TCR counterparts. As a final result, researchers developed a bispecific antibody constructed from H2 (H2- scDb) can activate T cells even when the pHLA complex is expressed at very low, endogenous levels. This promising research shows that MHC can be a key player in the fight against cancers caused by p53 mutations. <ref>DOI: 10.1126/science.abc8697</ref>. See below for interactive figures from this research.